Human Growth Hormone Secretagogue Receptor (GHSR), a member of the G Protein-Coupled Receptors (GPCR) family, was identified in 1996 as a 7 transmembrane domain 366 amino-acid protein that is responsible for the regulation of the growth hormone (GH) secretion. This receptor is mainly expressed in the hypothalamus, pituitary cells, and a number of peripheral tissues. Expression of the GHSR has been reported in various types of tumors, including breast carcinomas, prostate cancer cell lines, ovarian tumors, testicular tumors, pancreatic endocrine tumors, and intestinal carcinoids. The presence of high affinity and specific binding sites on GHSR in the neoplastic cells which are absent in the corresponding normal tissues has been demonstrated in at least 3 different human breast carcinoma cell lines and pancreatic endocrine tumors.
Ghrelin, as shown in FIG. 1, was discovered in 1999 by Kojima et. al. and is the natural ligand for the GHSR. Ghrelin is a 28-amino acid peptide hormone in which serine-3 residue is n-octanoylated. This hormone plays an important role in the stimulation of GH secretion through binding with GHSR along with some other functions including appetite regulation. Ghrelin binds to the GHSR with high affinity and specificity, resulting in a ghrelin-GHSR complex that is internalized.